1094-P: Short-Acting Exenatide and Markers of Cardiovascular Disease in Type 1 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Trial

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: JOHANSEN, NICKLAS J., DEJGAARD, THOMAS F., LUND, ASGER, SCHLÜNTZ, CAMILLA, LARSEN, EMIL LIST, POULSEN, HENRIK E., GØTZE, JENS P., MØLLER, HOLGER, VILSBØLL, TINA, ANDERSEN, HENRIK U., KNOP, FILIP K.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2020
• Subjects: Antidiabetics; Body fat; Body mass index; Body weight; Body weight loss; Brain natriuretic peptide; C-reactive protein; Cardiovascular disease; Cardiovascular diseases; Deoxyguanosine; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); DNA damage; Dual energy X-ray absorptiometry; Glucagon; Glucagon-like peptide 1; Health risk assessment; Injection; Insulin; Interleukin 2; Lean body mass; Oxidation; Peptides; Ribonucleic acid; RNA; Tumor necrosis factor-α
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-1094-P

In type 2 diabetes, some glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events. Whether GLP-1RAs have any effect on cardiovascular disease risk in patients with type 1 diabetes remains to be elucidated. We tested the effect of adding the short-acting GLP-1RA exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes.
In a randomized, double-blinded, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily insulin injection therapy with body mass index >22.0 kg/m2 and HbA1c 7.5-10.0% (59-88 mmol/mol) were randomized (1:1) to preprandial subcutaneous injection of 10 µg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported data were secondary endpoints and analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population.
Exenatide changed total fat mass by -2.6 kg (95% CI -3.6;-1.6, P<0.0001) and lean body mass by -1.1 kg (95% CI -1.9;-0.4, P=0.01) compared to placebo as assessed by dual-energy X-ray absorptiometry. Central and peripheral fat mass reductions were similar. Exenatide did not change levels of interleukin 2 or 6; tumor necrosis factor alpha; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (DNA oxidation marker).
Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction but had no effect on circulating biomarkers of cardiovascular disease risk.
Disclosure
N.J. Johansen: Research Support; Self; AstraZeneca. T.F. Dejgaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. C. Schlüntz: None. E. Larsen: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H.E. Poulsen: Research Support; Self; Boehringer Ingelheim International GmbH. J.P. Gøtze: None. H. Møller: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S.
Funding
AstraZeneca